title: Phase I-II clinical trial of oxaliplatin, fludarabine, cytarabine, and rituximab therapy in aggressive relapsed/refractory chronic lymphocytic leukemia or Richter syndrome.
abstract: BACKGROUND
  To improve outcomes of patients with Richter syndrome (RS) and relapsed/refractory chronic lymphocytic leukemia (CLL), we modified the OFAR1 regimen (oxaliplatin and cytarabine doses of the oxaliplatin, fludarabine, cytarabine, and rituximab) for this phase I-II study (OFAR2).
  
  
  METHODS
  OFAR2 consisted of oxaliplatin at 30 mg/m(2) on days 1 to 4, fludarabine at 30 mg/m(2), cytarabine at 0.5 g/m(2), rituximab at 375 mg/m(2) on day 3, and pegfilgrastim at 6 mg on day 6. Fludarabine and cytarabine were given on days 2 and 3 (cohort 1), days 2 to 4 (cohort 2), or days 2 to 5 (cohort 3) every 4 weeks. Phase II followed the "3 + 3" design of phase I.
  
  
  RESULTS
  The 102 patients (CLL, 67; RS, 35) treated had heavily pretreated high-risk disease. Twelve patients were treated in phase I; cohort 2 was the phase II recommended dose. The most common toxicities were hematologic. Response rates (phase II) were 38.7% for RS (complete response [CR], 6.5%) and 50.8% for relapsed/refractory CLL (CR, 4.6%). The median survival durations were 6.6 (RS) and 20.6 (CLL) months. Among 9 patients who underwent allogeneic stem cell transplantation (SCT) as post-remission therapy, none has died (median follow-up, 15.9 months).
  
  
  CONCLUSIONS
  OFAR2 had significant antileukemic activity in RS and relapsed/refractory CLL. Patients undergoing SCT as post-remission therapy had favorable outcomes.
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: atsimber@mdanderson.org.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
authors.forename: Xavier
authors.initials: X
authors.lastname: Badoux
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012008:Recurrence; D000069283:Rituximab; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009944:Organoplatinum Compounds; D003561:Cytarabine; D000077150:Oxaliplatin; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine
keywords: OFAR; Refractory CLL; Richter syndrome; SCT; Therapy